Repeatedly bred male and female rats develop arteriosclerosis, hypertension, diabetes, kidney stones, other degenerative changes, and age prematurely. These degenerative changes occur spontaneously and their incidence and severity appears to be related to the frequency and intensity with which these animals are bred. One of the outstanding common denominators in this "syndrome" of degenerative diseases and accelerated aging is the concomitant development of abnormal adrenocortical and medullary function. It is believed that the abnormal adrenal function which accompanies repeated breeding is related to alterations in lipid, carbohydrate and protein metabolism, as well as to abnormal connective tissue metabolism, and the sum total of these metabolic changes constitutes a framework of accelerated degeneration and aging. It is our plan to investigate the various hormonal metabolic changes which occur in connection with the reproductive effort, particularly as concerned with hypothalamic-pituitary-adrenal-gonadal activity. An attempt will be made to correlate changes in adrenal steroid production with specific changes in metabolism as they may, in turn, relate to specific degenerative changes and aging.